Insulin is one of the most important hormonal regulators of metabolism. Since the diabetes patients increase dramatically, the chemical properties, biological and physiological effects of insulin had been extensively studied. In last decade the development of NMR technique allowed us to determine the solution structures of insulin and its variety mutants in various conditions, so that the knowledge of folding, binding and stability of insulin in solution have been largely increased. The solution structure of insulin monomers is essentially identical to those of insulin monomers within the dimer and hexamer as determined by X-ray diffraction. The studies of insulin mutants at the putative residues for receptor binding explored the possible conformational change and fitting between insulin and its receptor. The systematical studies of disulfide paring coupled insulin folding intermediates revealed that in spite of the conformational variety of the intermediates, one structural feature is always remained: a "native-like B chain super-secondary structure", which consists of B9-B19 helix with adjoining B23-B26 segment folded back against the central segment of B chain, an internal cystine A20-B19 disulfide bridge and a short α-helix at C-terminal of A chain linked. The "super-secondary structure" might be the "folding nucleus" in insulin folding mechanism. Cystine A20-B19 is the most important one among three disulfides to stabilize the nascent polypeptide in early stage of the folding. The NMR structure of C.elegans insulin-like peptide resembles that of human insulin and the peptide interacts with human insulin receptor. Other members of insulin super-family adopt the "insulin fold" mostly. The structural study of insulin-insulin receptor complex, that of C.elegans and other invertebrate insulin-like peptide, insulin fibril study and protein disulfide isomerase (PDI) assistant proinsulin folding study will be new topics in future to get insight into folding, binding, stability, evolution and fibrillation of insulin in detail.

Insulin is a hormone that is essential for regulating energy storage and glucose metabolism in the body. Insulin in liver, muscle, and fat tissues stimulates the cell to take up glucose from blood and store it as glycogen in liver and muscle. Failure of insulin control causes diabetes mellitus (DM). Insulin is the unique medicine to treat some forms of DM. The population of diabetics has dramatically increased over the past two decades, due to high absorption of carbohydrates (or fats and proteins), lack of physical exercise, and development of new diagnostic techniques. At present, the two largest developing countries (India and China) and the largest developed country (United States) represent the top three countries in terms of diabetic population. Insulin is a small protein, but contains almost all structural features typical of proteins: α-helix, β-sheet, β-turn, high order assembly, allosteric T®R-transition, and conformational changes in amyloidal fibrillation. More than ten years' efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing, especially at the initial stage that forms the nascent peptide. Two structural switches are also known to regulate insulin binding to receptors and progress has been made to identify the residues involved in binding. However, resolving the complex structure of insulin and its receptor remains a challenge in insulin research. Nevertheless, the accumulated knowledge of insulin structure has allowed us to specifically design a new ultra-stable and active single-chain insulin analog (SCI-57), and provides a novel way to design super-stable, fast-acting and cheaper insulin formulations for DM patients. Continuing this long journey of insulin study will benefit basic research in proteins and in pharmaceutical therapy.
Allosteric Regulation ; Amino Acid Sequence ; Animals ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Insulin ; chemistry ; genetics ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Engineering ; Protein Folding ; Protein Stability ; Protein Structure, Tertiary ; Receptor, Insulin ; chemistry ; metabolism ; Surface Properties

Objective To investigate the display status of ultrasonography imaging check in central nervous system (CNS) in infants of early pregnancy and the diagnostic value of CNS malformation in infants of early pregnancy.Methods Gestational weeks of 2 751 enrolled subjects were divided according to the ultrasonic measurement of the crown rump length (CRL):11-11 +6 weeks group,12-12+6 weeks group,and 13-13 + 6 weeks group,prenatal ultrasound were performed to examine fetal CNS anatomy in infants of early pregnancy,record the display status in each groups of infants and analyze the relationship between the display situation and gestational age.Results Fourteen cases of fetal CNS malformation (20 malformations) in total were found by prenatal ultrasound,and the incidence of CNS malformation was about 5.09％ (14/2 571).Wherein,12 cases of early pregnancy were diagnosed,and 2 cases of middle pregnancy were diagnosed.The sensitivity of ultrasound of early pregnancy in the diagnosis of fetal CNS malformation was 85.71％.In the group of research,the ultrasound display ratios of 11-11+6 weeks group,12-12+6 weeks group and 13-13+6 weeks group were 96.73％,97.94％,98.06％,respectively.There was no significant difference in early pregnancy fetal CNS display ratio among groups (x2 =1.56,v =2,x2＜ x0.05.2 =5.99,P ＞ 0.05).Conclusions The display rate of CNS structure in infants of early pregnancy (11-13+6 weeks)is higher,and is not affected by gestational weeks.Prenatal ultrasound can effectively diagnose CNS severe malformation in infants of early pregnancy.

Objective: To investigate the differences of genotyping and virulence of hospital-acquired methicillin-resistant staphylococcus aureus (HA-MRSA) and community-acquired methicillin-resistant staphylococcus aureus (CA-MRSA). Methods: A total of 83 non-repetitive clinical specimens were collected in this study. All samples were classified into HA-MRSA and CA-MRSA according to the definition of the USA Centers for Disease Control and Prevention (CDC). Multiple polyemeras chain reaction (PCR) was used for SCCmec typing, and spa typing was conducted by means of PCR plus DNA sequencing. Panton-valentine leucocidin (PVL), phenol-soluble modulins α (PSMa), phenol-soluble modulins mec (PSM-mec), exfoliative toxin A (ETA), exfoliative toxin B (ETB), toxic shock syndrome toxin (TSST), α-toxin (hla), δ-toxin (hld) were also detected by conventional PCR. Results: The SCCmec type Ⅰ, Ⅱ, Ⅲ, Ⅳa and unclassified type accounted for 1.2%, 3.6%, 65.1%, 28.9% and 1.2%, respectively. 82.1% of the 39 strains of HA-MRSA were identified as SCCmec Ⅲ. While for the 44 strains of CA-MRSA, SCCmec Ⅲ and Ⅳa each accounted for 50%. The proportions of SCCmec Ⅲ and Ⅳa in HA-MRSA and CA-MRSA showed significant differences (χ²=9.343, 20.253, both P<0.05); There were 15 types of spa, t437, t062, t015 accounted for 39.8%, 21.7% and 10.8% respectively. Among the strains of HA-MRSA, the spa type t437 and t062 accounted for 28.2% and 23.1%, respectively, while for the spa type of CA-MRSA, t437 and t062 accounted for 50% and 20.5%, respectively. There was significant difference of t437 type between HA-MRSA and CA-MRSA (χ²=4.100, P=0.043). The positive rates of PSM-a, hla and hld were all 100%, and the positive rates of PVL, ETA, ETB, TSST and PSM-mec were 24.3%, 4.8%, 1.2%, 10.8% and 4.8%, respectively. The proportions of PVL positive HA-MRSA and CA-MRSA were 10.3% and 36.4%, respectively, which was significantly different (χ²=7.705, P=0.006), while PSM-mec positive HA-MRSA and CA-MRSA were 10.3% and 0%, respectively. Conclusions The strains of SCCmec Ⅳa and spa t437 are detected in HA-MRSA, suggesting that the more virulent CA-MRSA genotypes coexist with the traditional HA-MRSA genotypes in the hospital-acquired infections, which brings new challenges for the prevention and control of hospital infection.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.